Residual Paresthesia After Surgery for Degenerative Cervical Myelopathy: Incidence and Impact on Clinical Outcomes and Satisfaction.

STUDY DESIGN: Multicenter, prospective cohort study. OBJECTIVE: The current study aimed to identify the incidence of residual paresthesias after surgery for degenerative cervical myelopathy (DCM), and to demonstrate the impact of these symptoms on clinical outcomes and patient satisfaction. SUMMARY OF BACKGROUND DATA: Surgery for DCM aims to improve and/or prevent further deterioration of physical function and quality-of-life (QOL) in the setting of DCM. However, patients are often not satisfied with their treatment for myelopathy when they have severe residual paresthesias, even when physical function and QOL are improved after surgery. MATERIALS AND METHODS: The authors included 187 patients who underwent laminoplasty for DCM. All patients were divided into two groups based on their visual analog scale score for paresthesia of the upper extremities at one year postoperatively (>40 vs. ≤40 mm). Preoperative factors, changes in clinical scores and radiographic factors, and satisfaction scales at one year postoperatively were compared between groups. The authors used mixed-effect linear and logistic regression modeling to adjust for confounders. RESULTS: Overall, 86 of 187 patients had severe residual paresthesia at one year postoperatively. Preoperative patient-oriented pain scale scores were significantly associated with postoperative residual paresthesia ( P =0.032). A mixed-effect model demonstrated that patients with severe postoperative residual paresthesia showed significantly smaller improvements in QOL ( P =0.046) and myelopathy ( P =0.037) than patients with no/mild residual paresthesia. Logistic regression analysis identified that residual paresthesia was significantly associated with lower treatment satisfaction, independent of improvements in myelopathy and QOL (adjusted odds ratio: 2.5, P =0.010). CONCLUSION: In total, 45% of patients with DCM demonstrated severe residual paresthesia at one year postoperatively. These patients showed significantly worse treatment satisfaction, even after accounting for improvements in myelopathy and QOL. As such, in patients who experience higher preoperative pain, multidisciplinary approaches for residual paresthesia, including medications for neuropathic pain, might lead to greater clinical satisfaction. LEVEL OF EVIDENCE: 3.

Dynamics of Moiré Trion and Its Valley Polarization in a Microfabricated WSe2/MoSe2 Heterobilayer.

The moiré potential, induced by stacking two monolayer semiconductors with slightly different lattice mismatches, acts as periodic quantum confinement for optically generated excitons, resulting in spatially ordered zero-dimensional quantum systems. However, there are limitations to exploring intrinsic optical properties of moiré excitons due to ensemble emissions and broadened emissions from many peaks caused by the inhomogeneity of the moiré potential. In this study, we proposed a microfabrication technique based on focused Ga+ ion beams, which enables us to control the number of peaks originating from the moiré potential and thus explore unknown moiré optical characteristics of WSe2/MoSe2 heterobilayer. By taking advantage of this approach, we reveal emissions from a single moiré exciton and charged moiré exciton (trion) under electrostatic doping conditions. We show the momentum dark moiré trion state above the bright trion state with a splitting energy of approximately 4 meV and clarify that the dynamics are determined by the initial trion population in the bright state. Furthermore, the degree of negative circularly polarized emissions and their valley dynamics of moiré trions are dominated by a very long valley relaxation process lasting ∼700 ns. Our findings on microfabricated heterobilayer could be viewed as an extension of our groundbreaking efforts in the field of quantum optics application using moiré superlattices.

Risk Factors for Poor Outcome after Palliative Surgery for Metastatic Spinal Tumors.

Palliative surgery is performed to improve the quality of life of patients with spinal metastases. However, it is sometimes difficult to achieve the expected results because the patient's condition, and risk factors related to poor outcomes have not been well elucidated. This study aimed to evaluate the functional outcomes and investigate the risk factors for poor outcomes after palliative surgery for spinal metastasis. We retrospectively reviewed the records of 117 consecutive patients who underwent palliative surgery for spinal metastases. Neurological and ambulatory statuses were evaluated pre- and post-operatively. Poor outcomes were defined as no improvement or deterioration in functional status or early mortality, and the related risk factors were analyzed using multivariate logistic regression analysis. The results showed neurological improvement in 48% and ambulatory improvement in 70% of the patients with preoperative impairment, whereas 18% of the patients showed poor outcomes. In the multivariate analysis, low hemoglobin levels and low revised Tokuhashi scores were identified as risk factors for poor outcomes. The present results suggest that anemia and low revised Tokuhashi scores are related not only to life expectancy but also to functional recovery after surgery. Treatment options should be carefully selected for the patients with these factors.

Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians.

Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases1-3. Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3ß-hydroxysteroid dehydrogenase (3ß-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis.

The dual regulation of substance P-mediated inflammation via human synovial mast cells in rheumatoid arthritis.

BACKGROUND: Neural pathways are thought to be directly involved in the pathogenesis of rheumatoid arthritis (RA). Although synovial mast cells (MCs) are activated by substance P (SP), the role of MCs in neural pathways in RA remains unknown. The aims of this study were to investigate 1) whether tachykinins are produced by synovial MCs and whether production differs in RA and osteoarthritis (OA) patients, and 2) what is the responsible receptor for SP in synovial MCs. METHODS: Synovial tissues were obtained from patients with RA or OA undergoing joint replacement surgery. Cultured synovium-derived MCs were generated by culturing dispersed synovial cells with stem cell factor. SP expression was investigated using immunofluorescence and enzyme immunoassays. Mas-related gene X2 (MrgX2) expression was reduced in human MCs using a lentiviral shRNA silencing technique. RESULTS: SP expression was localized around the cell membrane in 41% (median) of the MCs in synovium from RA but in only 7% of that from OA, suggesting the activation of MCs. Synovial MCs expressed tachykinin (TAC) 1 mRNA, the expression of which was upregulated by the aggregation of FcɛRI or the addition of aggregated IgG. However, the released SP appeared to be rapidly degraded by MC chymase. Synovial MCs were activated with SP through MrgX2 to release histamine without producing proinflammatory cytokines. CONCLUSIONS: Activated synovial MCs may rapidly degrade SP, which may downregulate the SP-mediated activation of synoviocytes in RA. On the other hand, SP activates MCs to induce inflammatory mediators, suggesting the dual regulation of SP-mediated inflammation by MCs in RA.

Two Revision Surgeries on Cemented Custom-made Tumor Prostheses.

We performed revision surgery in 2 patients for stem fracture of a cemented tumor prosthesis that occurred more than 25 years after the initial surgery. For revision, the global modular replacement system (GMRS) was used. However, as bone cement in the bone could not be adequately removed, stems with respective diameters of 11 and 12.5 mm were used. In revision surgery for cemented tumor prostheses, adequate removal of residual bone cement is optimal. However, when there is a risk of fracture, it may be appropriate to insert a thicker stem after reaming the femoral canal as much as possible, and then fix the stem using the cement-in-cement method.

Lung squamous cell carcinoma with brachial soft tissue metastasis responsive to gefitinib: Report of a rare case.

Metastasis of lung cancer to soft tissue is rare and patient outcomes are generally poor. There are no reports describing soft tissue metastasis in lung squamous cell carcinoma (SCC), in which gefitinib treatment was effective not only for the primary tumor but also the metastatic lesion. A 61-year-old Asian woman presented to our facility with pain and a mass in the brachium. An additional tumor was identified in the lung. As we suspected soft tissue metastasis of lung cancer, an incisional biopsy was performed, yielding a diagnosis of SCC. The brachial tumor continued to grow and became exposed at the biopsy site when the incisional wound dehisced. Because the biopsied specimen was positive for an epidermal growth factor receptor (EGFR) gene mutation, we commenced gefitinib administration. This treatment resulted in the rapid shrinkage of both the brachial metastasis and the primary tumor, followed by healing of the wound. Therefore, tyrosine kinase inhibitors should be used for cases that present EGFR activating mutations independently from the presence of skin and soft tissue metastases.

Interleukin-33 synergistically enhances immune complex-induced tumor necrosis factor alpha and interleukin-8 production in cultured human synovium-derived mast cells.

BACKGROUND: Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-33 is believed to play an important role in the pathogenesis of RA. We recently reported that FcγRI is responsible for producing abundant tumor necrosis factor alpha (TNF-α) from cultured synovium-derived MCs (SyMCs) in response to aggregated immunoglobulin G (IgG). However, whether or not IL-33 affects immune complex (IC)-induced synovial MC activation remains unknown. This study sought to evaluate the effect of IL-33 on IC-induced synovial MC activation. METHODS: Cultured SyMCs were generated by culturing synovial cells with stem cell factor. ST2 expression was analyzed using FACS and immunohistochemical techniques. Mediators released from the MCs were measured using EIAs or ELISAs. RESULTS: SyMCs obtained from patients with RA or osteoarthritis (OA) expressed ST2 on their surfaces. We confirmed the expression of ST2 in MCs using immunofluorescence staining in joint tissue obtained from RA patients. IC-triggered histamine release was not enhanced by IL-33. However, IL-33 synergistically enhanced IC-induced IL-8 and TNF-α production in SyMCs. CONCLUSIONS: ICs and IL-33 may exacerbate inflammation associated with RA by abundantly producing TNF-α and IL-8 from SyMCs.

Refractory ulcer of reconstructed gastric tube after esophagectomy: a case report.

We report a case in which rabeprazole cured gastric tube ulcer after esophagectomy for esophageal squamous cell carcinoma (ESCC). A 47-year-old Japanese man was referred to our hospital with refractory ulcer of the reconstructed gastric tube one year after esophagectomy for ESCC. The ulcer proved refractory to healing by the administration of omeprazole or lansoprazole, or eradication of Helicobacter pylori after examinations concerning ischemia, acid over-secretion and H. pylori infection. Finally, metabolizer type was examined for proton pump inhibitors (PPIs), revealing the patient as a hetero-extensive metabolizer for the CYP2C19 genotype. This suggested sensitivity to rabeprazole, but resistance to omeprazole and lansoprazole. The refractory ulcer was subsequently cured after changing the PPI to rabeprazole. Examination of PPI metabolizer type might thus be important, along with an investigation of ischemia, acid secretion and H. pylori infection in the treatment of refractory gastric tube ulcer after esophagectomy.